The public health crisis of malaria-HIV co-infection is rapidly expanding in sub-Saharan Africa. Lowland western Kenya in particular is holoendemic for malaria transmission and is plagued with catastrophically high rates of HIV/AIDS infection. A 2006 mathematical model of transmission in this region retrospectively predicted that co-infection has resulted in a cumulative excess of 8,500 HIV-1 infections and 980,000 malaria episodes since 1980. Individuals infected with HIV experience more frequent and more severe episodes of clinical malaria and the risk increases with advancing HIV disease. However, our pilot studies and a significant body of published data also suggest that specific increases in asymptomatic parasitemias and gametocytemias also are likely to occur in HIV-infected individuals in malaria-holoendemic areas. While numerous studies have examined one or more of the complicating aspects of co-infection and symptomatic malaria in cross-sectional studies, no studies have attempted to determine the longitudinal epidemiological impact of co-infection on asymptomatic malaria and specifically on malaria transmission in regions characterized by high transmission of both diseases and by increasing antimalarial drug resistance. Antifolates are widely prescribed for prophylaxis of HIV-associated opportunistic infections, yet they are also known to increase the appearance of gametocytes. We hypothesize that co-infection with HIV, and associated therapy, could be directly responsible for significant increases in asymptomatic parasite carriage and gametocytemia as well as increased antifolate- resistant parasite genotypes and, therefore, contribute directly to the increased burden of falciparum malaria. To this end, we propose to focus complementary clinical and entomological studies using highly sensitive and specific molecular tools in a highly endemic area of western Kenya to assess point and longitudinal prevalence's of co-infection in general and gametocytemia in particular with an emphasis on longitudinal risk of malaria transmission in the context of prevailing HIV therapies. PUBLIC HEALTH RELEVANCE: HIV and malaria co-infection has resulted in increased clinical malaria prevalence, although the causes for this increase are incompletely understood. In our studies, we will examine a novel hypothesis that increased malaria burden in Kenya is due in part to enhanced mosquito-borne transmission of malaria from co-infected patients.